Norepinephrine links astrocytic activity to regulation of cortical state

Cortical state, defined by population-level neuronal activity patterns, determines sensory perception. While arousal-associated neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes remains unknown. Furthermore, general mechanisms regulating cortical synchrony in the wake state are poorly understood. Using in vivo imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization. We characterize astrocytes’ calcium responses to changes in behavioral arousal and NE, and show that astrocytes signal when arousal-driven neuronal activity is reduced and bi-hemispheric cortical synchrony is increased. Using in vivo pharmacology, we uncover a paradoxical, synchronizing response to Adra1a receptor stimulation. We reconcile these results by demonstrating that astrocyte-specific deletion of Adra1a enhances arousal-driven neuronal activity, while impairing arousal-related cortical synchrony. Our findings demonstrate that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-associated desynchrony to cortical circuit resynchronization.


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No statistical methods were used to predetermine sample size, but our sample sizes are similar to those reported in previous publications (Bojarskaite, 2020;Ding, 2019;Paukert, 2014;Reimer, 2014Reimer, , 2016, and statistical significance was calculated using post-hoc tests. Data exclusions No data was excluded from analyses except for the following (not pre-determined): In hSYN-hM4Di experiments, outliers were excluded across all conditions from small stationary responses to avoid confounding effects from other influences on astrocyte Ca2+, as described in methods. For in vivo pharmacology experiments, electrical artifacts in band power were excluded before analysis, as described in methods.

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